No validated protein signature is available that has been proved to be sufficiently useful in the clinic to stratify patients into groups that may be treated differently with radiotherapy. Many factors determine the biology of tumors and as such impact prognosis and survival outcome of cancer patients. TGF-β is a pleiotropic cytokine that is important in normal tissue homeostasis, regulates inflammation and immune responses, and controls proliferation and differentiation. TGF-β appears to be key in promoting epithelial-mesenchymal- transition (EMT), a process that leads to increased motility and invasion. Due to these oncogenic properties of TGF-β, several TGF-β signalling inhibitors are in preclinical and clinical trials to treat cancer. Radiotherapy is a corner stone of cancer therapy. There is substantial evidence that TGF-β plays a key role in the response to ionizing radiation. TGF-β is activated in irradiated tissues and plays a pivotal role in development of radiation induced fibrosis.